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Pharmaceutics 2018, 10(1), 21; https://doi.org/10.3390/pharmaceutics10010021

Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye: Failures, Successes, and Future Possibilities

Department of Ophthalmology, Mayo Clinic School of Medicine, 4500 San Pablo Rd., Jacksonville, FL 32224, USA
Received: 17 December 2017 / Revised: 15 January 2018 / Accepted: 23 January 2018 / Published: 27 January 2018
(This article belongs to the Special Issue Advanced Ocular Drug Delivery)
Full-Text   |   PDF [221 KB, uploaded 27 January 2018]

Abstract

Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of neovascularization and edema from several common chorioretinal vascular conditions. The intravitreally injected drugs (aflibercept, bevacizumab, conbercept, pegaptanib, and ranibizumab) used to treat these conditions improve the visual acuity and macular morphology in most patients. Monthly or bimonthly injections were administered in the phase III pivotal trials but physicians usually individualize therapy with pro re nata (PRN) or treat and extend regimens. Despite these lower frequency treatment regimens, frequent injections and clinic visits are still needed to produce satisfactory outcomes. Newly developed drugs and refillable reservoirs with favorable pharmacokinetic profiles may extend durations of action and require fewer office visits. However, we have learned from previous experiences that the longer durations of action seen in strategically designed phase III trials often do not translate to less frequent injections in real-life clinical practice. Unfortunately, long-acting therapies that produce soluble VEGF receptors (encapsulated cell technology and adenovirus injected DNA) have failed in phase II trials. The development of longer duration therapies remains a difficult and frustrating process, and frequent drug injections are likely to remain the standard-of-care for years to come. View Full-Text
Keywords: age-related macular degeneration; diabetic macular edema; extended duration therapy; intravitreal injections; vascular endothelial growth factor age-related macular degeneration; diabetic macular edema; extended duration therapy; intravitreal injections; vascular endothelial growth factor
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Stewart, M.W. Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye: Failures, Successes, and Future Possibilities. Pharmaceutics 2018, 10, 21.

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